1. Field of the Invention
The present invention relates to methods for defining genomic subgroups of tumors, cancer cell lines and subject samples related to non-small cell lung carcinoma (NSCLC). The present invention also relates to methods for assembling panels of tumors, cancer cell lines and subject samples according to genomic subgroups for use in testing the efficacy of one or more therapeutic interventions for administering to a subject.
2. Description of Related Art
Cancer is a disease of the genome characterized by substantial variability in clinical course, outcome, and therapy responsiveness. The main factor underlying this variability is the genetic heterogeneity innate to cancers. Individual tumors of the same histopathological subtype carry different aberrations in cellular DNA.
NSCLC is the most common cause of cancer-induced mortality worldwide (Parkin, 2001). Currently, NSCLC is characterized by histology—visual inspection of cell anatomy under a microscope, often coupled with various staining procedures to highlight specific physical characteristics of the cells. The major histologic subtypes of NSCLC are adenocarcinomas (the most common form of lung cancer), squamous cell lung carcinomas (SQ), and large-cell lung carcinomas (LCLC) (Travis and Sobin, 1999). About 40% of patients with early-stage NSCLC relapse within five years after surgical removal of the tumor {Hoffman, 2000 #39}. Current therapeutics for treating NSCLC are efficacious only in a fraction of patients, highlighting the fact that NSCLCs differ from each other. Tumors within the same histopathological groups follow significantly different clinical courses and respond differently to therapy. The current histology-based staging of NSCLC is therefore inadequate for predicting the clinical course of the disease or treatment outcome.
The phenotypic diversity of lung tumors is accompanied by a corresponding diversity in gene copy number aberration patterns. Chromosomal aberrations are detrimental events associated with a number of developmental diseases and cancer. Chromosomal region amplifications and deletions in somatic cells are believed to be one of the main factors leading to cancer. Systematic examination of gene copy number patterns in lung cancer might then serve as a foundation for a genomics-based molecular taxonomy of lung cancers. Recurrent chromosomal aberration of prognostic significance can be detected individually by classical cytogenetic analysis or fluorescent in situ hybridization (FISH) (Levsky and Singer, 2003). However, FISH analysis cannot detect the entire spectrum of genetic abnormalities as it only interrogates a limited set of chromosomal loci defined by the applied probe panel. A more advantageous diagnostic tool would be based on a refined classification of the disease. It would enable rational patient selection for treatment based on the genetic status of a subject's NSCLC.